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Most exercise testing is performed in adults with known or suspected ischemic heart disease. In the last few years cardiac imaging techniques have been applied in this field, improving the information obtained with the procedure. However, the exceptions to this rule are emerging rapidly not only in healthy people (asymptomatic individuals, athletes, handicapped people) but also in cardiac patients (advanced congestive heart failure, hypertension, rhythm disorders, congenital heart disease, etc.). All the-se issues justify the need for a multidisciplinary consensus document in Spain. This paper reviews and updates the methodological aspects of the stress test, including those related to oxygen consumption measurements. The main aim of this review was to determine the role of exercise testing in the evaluation of ischemic heart disease as well as the applications of imaging stress testing. The usefulness of this test in other non-ischemic cardiac disorders and in selected subsets of healthy people is also reviewed.

We describe the thrombophilic and clinical characteristics of a group of patients who suffered venous thrombosis (VT) (n = 36) and ischemic stroke (n = 8) while taking oral contraceptives (OC). Our purpose is to ascertain whether there are differences between users of second and third generation progestogen and to investigate the influence of concurrent congenital and acquired risk factors (other than OC) on the onset of the thrombosis. The group of patients included 36 women with VT and eight with ischemic stroke. The patients' recognized predisposing factors were recorded. We also considered age, length of time on OC, types of OC, rethrombosis, family history of VT, and the presence of thrombophilic genetic defects. In the group of patients with VT, 54% were treated with second generation OC (n = 23), and 30% (n = 11) were treated with third generation OC. We found no significant statistical differences with respect to age and length of time on OC between the two types of OC. The prevalence of genetic defects in these patients--factor V (FV) Leiden, prothrombin G20210A mutation and protein S deficiency--was 19% (n = 7), 17% (n = 6), and 8% (n = 3) respectively. We observed the shortest time lapse between initiating OC and the first thrombotic event in carriers of FV Leiden and in patients with combined defects, but the differences were not significant. In patients with ischemic stroke, 50% were treated with second generation OC and 50% were treated with third generation OC. Prothrombin G20210A mutation was detected in two patients. In both patients,the stroke occurred earlier than in the rest of the patients, but these differences were not statistically significant. With respect to preventing thrombotic events in these patients, our data suggest that OC therapy should be avoided in patients with a previous history of thrombosis and in patients with an evident thrombotic tendency in the family. In patients in whom the family history of thrombosis is not very evident, it would be recommended to screen for FV Leiden, prothrombin G20210A mutation, and protein S, and to rule out OC if the patient does in fact have one of these risk factors. Moreover, if a patient develops a thrombotic complication while taking OC, an evaluation to search for a thrombophilic defect is warranted, and at the same time, alternative methods of contraception should be considered.

A D-dimer assay can be helpful to rule out thromboembolism provided it is sensitive, reliable, fast and easy to perform. Tests based on the ELISA methodology have a high diagnostic sensitivity, and are therefore adequate for excluding deep venous thrombosis (DVT). The drawbacks are their long assay times, unsuitability to be run on single samples and cost. New methods have been developed, based either on the same principle, by immunofiltration or by microlatex immunoturbidimetric assays which seem to reach the high sensitivity and negative predictive value (NPV) required, but allowing fast and quantitative single sample analysis. The aim of this work was to evaluate one rapid test, a fully automated quantitative assay (IL Test D-dimer, run on an ACL 7000 coagulation analyzer, Instrumentation Laboratory).We compared the diagnostic value of IL Test for DVT with that of an ELISA (Dimertest Gold EIA Agen Biomedical Limited, Acacia Ridge, Australia). Eighty-six patients (43 men, 43 women, mean age: 61 years) showing DVT symptoms formed the population for this non-randomized controlled trial in a referral center. The diagnosis of DVT based on the clinical history, was confirmed by serial compression ultrasonography (CUS) with Doppler flow in 62 patients.The IL Test D-dimer proved to be rapid, automated and well suited for individual tests with a good reproducibility in three control plasmas with different concentrations of D-dimer (coefficient of variation range 0.54-3. 87%). Its performance was comparable to that of the Dimertest Gold EIA, as indicated by the areas under the receiver operating characteristic curves (Dimertest Gold EIA 0.748; IL Test D-dimer 0.70). On the basis of kappa coefficients, there was a good concordance between the Dimertest Gold EIA and IL Test D-dimer when the receiver operating characteristic (ROC) curves suggested cut-offs were used. The sensitivity (98.3%) and NPV (88.9%) shown by IL Test D-dimer are comparable or even better than those obtained for EIA (95%, 80%, respectively).This study shows that the new method can be included in prospective clinical trials to test the utility of D-dimer measurement in combination with other non-invasive diagnostic procedures in the management of DVT diagnosis.

Thrombosis occurs in 20 to 30% of patients with Behçet's disease (BD), but the precise pathogenic mechanism underlying the thrombotic tendency in these patients is not well known. Venous thromboses are commonly located in the lower extremities, but right intracardiac thrombi are extremely rare. We report for the first time on a young patient with BD associated the 20210G-A prothrombin gene mutation and right intracardiac thrombosis. We suggest that the association of BD with this newly recognized prothrombotic genetic mutation may have contributed to the development of the thrombotic event in this patient.

The effect of local and circulating thrombin on platelet adhesion onto vascular surfaces was explored in the absence of plasma adhesive proteins using flow conditions.To study the local effects of thrombin, denuded rabbit aorta segments were incubated with thrombin concentrations of 0.001, 0.01 and 0.1 U/mL. To evaluate the effects of circulating thrombin, the same concentrations were added to perfusates consisting of washed platelets and washed red blood cells suspended in a human albumin solution (5%). In some experiments, purified von Willebrand's factor (vWF) (Haemate-P) was added to the perfusates (0. 8 U/mL of vWF, final concentration). A humanized chimeric antibody to the GPIIb-IIIa complex (Reopro) was used to determine the role of this glycoprotein on platelet adhesion under the conditions described. The effect of blocking GPIb was also assessed. Perfusions were carried out at 800 s(-1) for 10 min. The interaction of platelet with the vessel surface was morphometrically evaluated and expressed as percentage of surface coverage (%SC). Changes in the surface expression of the major platelet antigens were also analyzed by flow cytometry.Incubation of subendothelial surfaces with thrombin enhanced platelet deposition with respect to control levels (increases in SC of 64%, 79% and 86% with 0.001, 0.01 and 0.1 U/mL of thrombin, respectively). Low concentrations of thrombin (0.001 and 0.01 U/mL) incorporated in the perfusates resulted in a similar pro-adhesive effect (increases in SC of 64% and 71%, respectively) while the highest concentration (0.1 U/mL) failed to produce a pro-adhesive effect due to the augmented formation of platelet aggregates with subsequent thrombocytopenia (15+/-1 vs. 160+/-5x10(9) plt/L in the perfusates). Similar results were obtained when VWF was present in the perfusate. Reduction of platelet deposition by blockade of GPIIb-IIIa (to 5.3+/-0.7%) was partially restored by thrombin. Blockade of GPIb prevented platelets from adhering even when thrombin was present (%SC of 2.0+/-0.8%). No significant changes in the distribution of platelet membrane glycoproteins during perfusion experiments were detected.Our results suggest that thrombin facilitates primary platelet adhesion onto vascular surfaces even in the absence of plasma adhesive proteins. This effect seems to be mainly dependent on the GPIb/vWF axis.

To study the usefulness of the complexed-to-total (C:T) prostate-specific antigen (PSA) ratio in the early detection of prostate cancer in patients with a total PSA value4.0 ng/ml.Total PSA and PSA complexed to alpha(1)-antichymotrypsin were measured in plasma from 193 men with benign prostatic hyperplasia (BPH) and 34 with prostate cancer. The diagnosis was confirmed in 28 BPH and 16 prostate cancer patients by biopsy and in 165 BPH and 18 prostate cancer patients by histological study following transurethral prostatectomy or open prostatectomy.The area under the receiver operating characteristic (ROC) curve was significantly greater for the C:T PSA ratio (0.908) than for total PSA (0.692) (p0.001). Using a cut-off point of 0.83 for the C:T PSA ratio and regardless of the digital rectal examination (DRE) finding, 20 of the 34 prostate cancer patients would have been given a correct diagnosis (59% sensitivity) and in only 8 of the 193 BPH patients would a biopsy have been necessary (96% specificity). With a cut-off of 0.79, the sensitivity increased to 85% with a specificity of 92%. When the analysis was restricted to the 44 patients with abnormal DRE, the area under the ROC curve for the C:T PSA ratio was 0.919, and a cut-off point of 0. 78 gave a sensitivity of 87% and a specificity of 93%. Using a cut-off of 0.63, all prostate cancers were detected (100% sensitivity) and 54% of the negative biopsies would have been eliminated. For the 183 patients diagnosed following surgery, a cut-off of 0.82 gave a sensitivity of 72% and a specificity of 94%.Our results show that the C:T PSA ratio significantly improves the clinical utility of the PSA assay for detecting prostate cancer in patients with total PSA4 ng/ml, increasing the sensitivity without significantly increasing the number of biopsies.

The effect of a binifibrate (Biniwas Retard, Wasserman) on the plasma lipids and hemorheological profile of 30 primary hyperlipemic patients was studied. Our results indicate that the patients under study had evident rheological alterations as well as the expected lipid alterations. Treatment with Biniwas (2 x 550 mg/day) for six months not only substantially improved the alterations in the lipid balance but also tended to normalize the patients' hemorheological alterations, and there was a statistically significant correlation between the two effects. Apart from the decrease in plasma viscosity (1.20 +/- 0.05 vs 1.29 +/- 0.07 mPa.s, p0.001), the most noteworthy effects of Biniwas treatment were the decrease in red blood cell aggregability (8.7 +/- 1.2 vs 9.3 +/- 1.1, p0.05) and increased deformability (55 +/- 3 vs 47 +/- 5%, p0.001). Both changes may be due to modifications in the lipid composition of the erythrocyte membrane due to cell-plasma lipid exchange.

The rheological profile of 45 patients who had kidney failure and were undergoing periodical hemodialysis was studied to ascertain whether they showed rheological alterations and if these alterations improved after hemodialysis. Our results indicate that the patients studied suffer rheological alterations with respect to the control group, specifically increased plasma fibrinogen (436 +/- 119 vs 271 +/- 43 mg/dl, p0.001), increased plasma viscosity (1.30 +/- 0.10 vs 1.22 +/- 0.05 mPa.s, p0.001), higher erythrocyte aggregability (8.3 +/- 1.2 vs 7.4 +/- 1.4, p0.01) and a lower hematocrit (31.2 +/- 5.9 vs 43.4 +/-3.7, p0.001). In contrast, erythrocyte deformability did not seem to be altered with respect to the control group. The analyses carried out immediately after hemodialysis showed that in general the rheological profile worsened during this treatment; there was a significant increase in fibrinogen and in plasma viscosity. The rheological alterations detected may play a role in the development of the atherosclerosis processes often experienced by these patients.

Dead specimens of Corynosoma cetaceum were used to describe the trunk musculature of this species and to infer the use of the trunk as a secondary holdfast. Inferences were based on trunk muscle arrangement, changes in trunk shape, size and distribution of spines, and geometry of tegument thickness. The foretrunk of C. cetaceum is swollen and forms a spiny disk that is bent ventrally. The disk is flattened by several groups of muscles not described previously, which seem able to finely adjust the disk surface over the substratum. Disk attachment appears to be accomplished by two dorsal neck retractor muscles specialized in pulling the anchored proboscis into the foretrunk. This mechanism has been described in other acanthocephalans, becoming surprisingly efficient when used with a flattened, armed foretrunk. The ventrally spined hindtrunk requires force to move downwards in order to attach. A single ventral neck retractor muscle seems specialized in pulling the posterior trunk forward, inducing a downward force due to the muscle's precise points of insertion. This mechanism necessarily generates ventral wrinkling that needs to be eliminated for the spiny surface to be functional. The trunk ventral muscles are apparently arranged so as to concentrate the "excess" of the tegument into a single fold, optimizing the use of the remaining surface for attachment. The size and distribution of spines, as well as the geometry of tegumental thickness, conform to these observations. Morphological changes, seemingly simple, such as structural bending, may have triggered a cascade of subtle modifications and new functions during acanthocephalan evolution, reflecting how morphological integration and novelty interact.

In order to ascertain whether young asymptomatic patients with heterozygous familial hypercholesterolemia (FH) but without clinical signs of atherosclerosis have increased plasma thrombomodulin (TM) levels expressing early endothelial damage, we determined TM in 23 heterozygous FH subjects (aged 28-44 years, x: 32 +/- 6) and in a well matched control group (CG). In addition, carotid Doppler ultrasonography was done in all the patients and controls in order to assess the state of the vascular tree. Results show a tendency for FH subjects to have higher TM values than the CG (37.8 +/- 14.2 ng/ml vs. 30.1 +/- 11.2 ng/ml), although the differences are not statistically significant. When taken together the results of TM and carotid ultrasound, the sensitivity and specificity of the former were only 66% and 80%, respectively. The fact that only 66% of the FH patients with atherosclerotic injury had high TM values eliminates the possibility of using this as an early marker of atherosclerosis in FH individuals.

Epidemiological studies suggest that hormone replacement therapy (HRT) decreases the risk of cardiovascular disease in postmenopausal women via several mechanisms, including modifications in the fibrinolytic system and lipoprotein(a) [Lp(a)] levels. The aim of this study was to examine the influence of the levels and isoforms of Lp(a) on fibrinolytic activity in 91 postmenopausal women in comparison with premenopause and analyze the effect of HRT on those parameters. In postmenopause, an increase in plasma Lp(a) and plasminogen activator inhibitor-1 (PAI-1) levels was found. A significant inverse correlation was observed between Lp(a) or PAI-1 levels and plasmin generation. Plasma samples with low molecular weight (MW) apo(a) isoforms showed higher plasmin inhibition than plasmas with high MW apo(a) isoforms and similar levels of total Lp(a) and PAI-1. HRT induced a significant decrease in Lp(a) and PAI-1 levels and an increase in estradiol levels, as well as an increase in fibrinolytic activity. A significant correlation was found between the percentages of variation in Lp(a) levels and in plasmin generation and between the percentages of variation in PAI-1 levels and in the euglobulin lysis time under HRT. In conclusion, the increase in fibrinolytic activity observed in women under HRT could be explained by two independent mechanisms: (a) the decrease in PAI-1 and (b) the decrease in the inhibition of plasmin generation due to the decrease in Lp(a) levels.

Increased circulating levels of type 1 plasminogen activator inhibitor (PAI-1) have been associated with coronary artery disease (CAD). However, genetic and environmental determinants of PAI-1 expression are only partially understood. The levels of PAI-1 have been found to relate to 4/5 guanosine (4G/5G) polymorphism in the promoter region of the PAI-1 gene. The 4G allele in this polymorphism has been associated with higher levels of plasma PAI-1 activity, but despite the strong correlation between PAI-1 activity and antigen, no association has been found between PAI-1 antigen levels and the PAI-1 promoter 4G/5G genotype. The aim of the present study was to analyze the influence of the PAI-1 promoter 4G/5G genotype on PAI-1 levels in post-menopause women with coronary disease in comparison with healthy women in pre and postmenopausal status, and the influence of this genotype on variations in PAI-1 levels after hormone replacement therapy (HRT). No differences between 4G/5G allele distribution in the groups studied were observed. The group of postmenopausal women with CAD showed significantly increased PAI-1 antigen and activity levels in comparison with the control groups, and the levels of PAI-1 correlated with the 4G/5G genotype. A multivariate analysis revealed that in the CAD group there was a high correlation between 4G allele dosage and PAI-1 antigen levels, which were also influenced by the triglyceride levels but not by estrogen or glucose levels. After hormone replacement therapy the decrease in PAI-1 levels was correlated with the 4G allele dosage. We conclude that in the group of postmenopausal women with CAD the influence of the PAI-1 promoter 4G/5G genotype on PAI-1 levels is more evident than in the control groups, and that the decrease in PAI-1 levels after HRT in CAD women correlates with the 4G allele dosage.

We describe the case of a 39-year-old woman who suffered two iliofemoral venous thromboses, a cerebral ischemic infarct and recurrent fetal loss. Initial studies showed high levels of antiphospholipid antibodies (APAs) and a moderate thrombocytopenia. After her second miscarriage, laboratory diagnosis revealed that the woman was heterozygous for the factor V Leiden mutation and had a functional protein S deficiency as well as anti-protein S and anti-beta 2-glycoprotein I antibodies. The impairment of the protein C pathway at various points could well explain the recurrent thromboses in the patient and supports the role of a disturbed protein C system in the pathophysiology of thrombosis in patients with APAs.

Deep vein thrombosis (DVT) seems to be related to a hypercoagulation and definite hemorheological alterations, but the importance of these alterations in the development of thrombotic events in the deep vein system has not been established. The present study examines both aspects in a group of 55 patients with DVT; the presence of a hypercoagulable state was assessed by quantifying the prothrombin fragment 1+2 (F1+2) and the thrombin-antithrombin III complex (T-AT), and the main hemorheological parameters were evaluated in the acute state and 6 and 12 months later. The results show marked hemorheological, F1+2, and TAT alterations in the acute phase. After 12 months the pattern shows a modest improvement, but erythrocyte aggregation, fibrinogen, F1+2 and T-AT remain increased with respect to the control group (8.51 +/- 1.43; 331 +/- 81 mg/dl; 1.33 +/- 0.60 nmol/l; 3.54 +/- 1.71 ng/ml vs. 8.10 +/- 1.40; 230 +/- 38; 0.94 +/- 0.40; 1.56 +/- 0.59, respectively). These data suggest that the thrombotic event could be influenced by the previous rheological situation and hypercoagulable state.

Characterization and frequency of the rpoB gene mutations associated with rifampin resistance in Mycobacterium tuberculosis clinical isolates in Sevilla.Characterization of rpoB mutations in 21 rifampicin-resistant strains of M. tuberculosis isolated during a three-year period (1994-1996) by three different molecular methods: a nonradioactive Single-strand conformation polymorphism (SSCP) analysis, DNA sequence analysis and a commercial method the line probe assay InnoLiPA.Five distinct rpoB mutations were identified. Ser531--Leu mutation was detected in 14 strains (66.7%), H526--Asp in 3 strains (14.3%), Ans512--Ser in 1 strain (4.8%), Glu513--Leu in 1 strain (4.8%). A nine nucleotide deletion (codon 510-513) was found in one strain (4.8%) while in the remaining resistant strain (4.8%) no mutation was detected.The frequency of the different mutations found in the rpoB gene, associated with rifampicin resistance in Mycobacterium tuberculosis clinical isolates in Seville, are similar to those previously reported. However, two new mutations has been detected: a nine nucleotide deletion (codon 510-513), and the Asn512--Ser point mutation. The characterization of the mutations in the rpoB gene could serve as epidemiological marker for the rifampicin resistant clinical isolates of M. tuberculosis.

In order to ascertain whether polygenic hypercholesterolemia (PH), the most common cause of small increases in plasma lipids during childhood, is associated with rheological alterations, we determined the hemorheological and lipid profile of 21 PH children (12 males, 9 females) and a well-matched control group (CG). In addition, a carotid ultrasound was done on all the PH children, but showed no alterations. When compared with the CG, PH children showed increased erythrocyte aggregation both at stasis (EAM0) (4.39+/-1.15 vs. 3.75+/-1.02), p0.05, and at low shear rate (EAM1) (8.22+/-1.42 vs. 7+/-1.39), p0.01, and increased plasma viscosity (PV) (1.19+/-0.04 cP vs. 1.15+/-0.04 cP), p0.01. These results reinforce the hypothesis that lipid metabolic alterations are associated with specific rheological modifications in absence of a demonstrable atherosclerotic lesion.

Commercial glass fibres were calcinated for the removal of organic matter, activated for surface silanol regeneration and silanizated with γ-aminopropyltri-ethoxysilane. Two different activation methods were used: reflux with neutral water and reflux with 10% HCl aqueous solution. Acid treatments hydrolize Si–O bonds, greatly changing the composition of the glass and regenerating silanol groups, some of them being of intraglobular nature. Water treatment does not change appreciably the glass composition, but its surface free energy value is the lowest. The degree of silanization is the greatest for the acid activated samples and the lowest for the water activated one. The polar contribution to the total surface free energy, once the samples are silanizated, is the highest for the fibres activated with boiling water whilst the dispersion component is about the same for all of them. SEM observations indicate that for the greatest degree of coating, debonding of the filaments may induce a peeling-out fractural mechanism. The authors wish to thank CICYT (MAT 930823) for financial support.

In order to ascertain whether hemorheological alterations precede the atherosclerotic lesion in familial hypercholesterolemia (FH), we studied the lipid and hemorheological profile of 29 heterozygous FH children (12 males and 17 females), aged 12+/-3 years, and a well-matched control group (CG), and assessed their plasma thrombomodulin level as an early marker of endothelial injury. No differences were found between FH children's plasma thrombomodulin values (31.7+/-11.2 ng/ml) and those of the CG (27.8+/-15 ng/ml). However, the rheological variables of FH children and the CG were statistically different (p0.001) for fibrinogen (Fbg): 266+/-48 mg/dl vs. 205+/-32 mg/dl; erythrocyte aggregation at stasis (EAM0): 4.6+/-1.2 vs. 3.3+/-0.9; erythrocyte aggregation at low shear (EAM1): 7.9+/-1.7 vs. 6.1+/-0.8; and plasma viscosity (PV): 1.18+/-0.03 cP vs. 1.12+/-0.04 cP. Correlations between rheological parameters and lipids were found. The normal values obtained in FH children for plasma thrombomodulin suggest that the hemorheological alterations appear prior to the vascular injury, are in part related to dyslipemia and could contribute to the development of the atherosclerotic process by modifying blood flow conditions.

In order to ascertain whether young familial hypercholesterolemic subjects without atherosclerotic lesions demonstrable on a carotid echo-Doppler show decreased erythrocyte deformability, we determined the erythrocyte elongation index (EEI) by means of a shear stress diffractometer (Rheodyn SSD) in twenty-four children with heterozygous familial hypercholesterolemia (FH), aged 12 +/- 3 years, and their corresponding affected parent. The parents were twenty-three adults with heterozygous FH aged, 32 +/- 6 years. The control group was made up of a similar number of well matched healthy volunteers. The EEI at 6, 12, 30 and 60 Pa showed no statistical differences between FH children and their control group, or between FH parents and their control group. No correlations were found between EEI and plasma lipids or lipoproteins at any of the shear stresses used. These results suggest that the red blood cells of young familial hypercholesterolemic subjects who show no deterioration of the vascular tree are not less deformable than those of healthy normolipemic subjects, and that dyslipemia itself does not produce alterations that damage the rheological properties of the red blood cell.

The cholesterol/phospholipid ratio (C/PL) of the red blood cell membrane, plasma lipids and erythrocyte aggregability were evaluated in 20 children with familial hypercholesterolemia (age: 10.4+/-4.6 years) but without detectable vascular injury. The results indicate that hypercholesterolemic children have a higher erythrocyte membrane C/PL ratio than the control group (0.81+/-0.23 vs. 0.65+/-0.08, p0.01). This membrane lipid alteration correlates inversely with the plasma concentration of HDL-cholesterol (r = -0.558, p0.010). The patients also showed greater erythrocyte aggregability than the control group (8.21+/-1.11 vs. 6.25+/-1.24, p0.001), but this does not seem to correlate with the changes observed in the lipid composition of the cell membrane. These results suggest that from childhood, people with familial hyper-cholesterolemia show alterations in the lipid composition of the red blood cell membrane that are related to the changes observed in plasma lipids and appear prior to atherosclerotic vascular symptoms.

In order to ascertain whether the increased aggregability observed in the red blood cells of diabetic patients is induced exclusively by plasma factors or is also influenced by membrane lipids, we examined the phospholipids of the erythrocyte membrane, the plasma fibrinogen concentration and erythrocyte aggregation in 86 insulin and non insulin-dependent diabetic patients. The data obtained show that the erythrocyte aggregability of the diabetic patients is higher than that of the control group (10.0+/-2.4 vs. 7.8+/-1.6%). This increased aggregability correlates not only with a higher fibrinogen concentration but also with changes observed in the membrane phospholipids. The percentage of sphingomyelin (SP) in the patients is higher than in the controls (22.6+/-6.8 vs. 18.4+/-5.4%) and that of phosphatidylserine (PS) is lower (9.5+/-6.1 vs. 12.1+/-5.1%). No differences in the percentages of the other two phospholipids identified (phosphatidylcholine, PC, and phosphatidylethanolamine, PE) were observed. The increase in the saturated nature of the phospholipids of the erythrocyte membrane, which can be measured by the (SP + PC)/(PE + PS) ratio, is statistically related (r = 0.39; p0.05) to the increased red blood cell aggregability observed in these patients.

It has been observed that the apo(a) isoforms of low molecular weight predict the family history of premature ECV. Our objective was to study the relationship between the levels of Lp(a) and the isoforms of apo(a) in parents and children.Twenty-four families, where at least one of the children had been diagnosed with familial or polygenic hypercholesterolemia and at least one of these children and one parent had Lp(a)or = 30 mg/dl, were studied. They were classified according to whether Lp(a) wasor =30 mg/dl, with 44 and 38 subjects in each group, respectively. The total cholesterol, triglycerides, HDL and LDL, the Lp(a) and apo(a) isoforms were determined, as well as the relative concentration of the latter.The molecular weight average of the major isoform was lower in the group with high Lp(a) levels (592 +/- 38 vs 656 +/- 65 kD, p0.001). An inverse correlation between Lp(a) levels and the major isoform size was found (r = -0.522, p0.001). The correlation of the Lp(a) levels in the child with that of his or her "best fit" (the best fit parent was that whose level was closer to that of the child) was very significant (r = 0.61, p0.01), but lower than the corresponding paternal apo(a) isoform levels (r = 0.801, p0.01). The study of the apo(a) isoforms in parents and their children suggests not only that the isoform is inherited, but also its concentration.Subjects with small size apo(a) isoforms have higher Lp(a) levels. There is a better correlation between parents and children in the phenotypes of the apo(a) than in Lp(a) levels. The determination of these parameters allows the identification of a risk population.

Editor,—I read with interest the article published in the BJO by Hunt.1 In this paper the author reports that the prevalence of APC resistance is more common than any other known thrombophilic state and was present in over one third of patients younger than 45 years with central retinal vein occlusion (CRVO). Therefore, many would argue that a full thrombophilia screening should be performed in a young patient …

Richness and composition of gastrointestinal helminth communities of 54 loggerhead turtles, Caretta caretta, from the western Mediterranean were interpreted from patterns of helminth exchange at 2 host taxonomic scales: exchange between marine turtles and other marine hosts and exchange within turtles. We predicted exchange of the former to be unimportant ecologically and evolutionarily because of the host phylogenetic distance. The absence of records of successful exchange at this host taxonomic scale confirmed that host physiological barriers seem to prevent contemporary parasite transfer between marine turtles and other sympatric hosts. Marine turtles also seem to exhibit an evolutionary association with their parasites largely independent from that of other marine hosts. Therefore, the composition of gastrointestinal helminth communities of marine turtles is predictably restricted to digeneans, nematodes, and aspidogastreans specific to these reptiles. At the scale of host species, helminth exchange among marine turtle species was expected to be significant. This was suggested by reports indicating a high proportion of parasites common to all sea turtle species. Mediterranean C. caretta harbored only 4 digenean species typical of marine turtles, and immature individuals of 1 digenean species accidentally acquired. Further, no relevant parasite exchange with other marine turtles was expected to occur because C. caretta is the only sea turtle species abundant in the western Mediterranean. Therefore, a predictable composition coupled with low species richness in infracommunities might be accounted for partly by constraints on parasite acquisition at both host scales. Host factors limiting parasite recruitment (mainly ectothermy and a wandering behavior) may also contribute to depauperate and isolationist infracommunities.

Investigation of the urethral flora in men with urethritis, with particular reference to anaerobic bacteria.Multiple cultures were performed on three urethral samples from 110 men attending the STD Clinic of the School of Medicine in Seville: 35 with no evidence of urethritis (control group), and 75 with urethritis (17 gonococcal urethritis (GU) and 58 non-gonococcal urethritis (NGU)). In the 58 men with NGU, Chlamydia trachomatis was isolated in 16 (27.5%), Ureaplasma urealyticum in 18 (31%), Trichomonas vaginalis in two (3.4%) and no pathogens were isolated in the remaining 22 (38%) patients.Aerobic flora, mainly Staphylococcus spp., were isolated less frequently (41%) in patients with GU than in the control group (80%), and those with NGU (72%). Anaerobic flora were isolated in 62% of patients, with similar isolation rates in each group. Gram-negative anaerobes were more frequently isolated in men with urethritis, especially NGU, compared to controls (P0.05). Prevotella spp. and Bacteroides spp. were significantly more frequently isolated in patients with NGU, including Chlamydia-negative NGU. Fusobacterium spp. were more frequent in the Chlamydia-positive NGU than in the controls (P0.05). P. magnus was the most frequent anaerobic species found in the control group, while P. prevotii was most frequently seen in the urethritis group. B. ureolyticus, P. prevotii and P. tetradius were more frequent on the NGU group (P0.05). B. ureolyticus was commoner in patients with Chlamydia-negative NGU, while P. tetradius and P. asaccharolytica was commoner in those where C. trachomatis was isolated than in the control group.Urethral microflora isolated showed ten bacterial genus and 25 different species of anaerobes. The spectrum of these microflora changed with the presence of urethritis and varied with its aetiology.

Increased levels of lipoprotein (a) [Lp(a)] have been considered an independent risk factor for cardiovascular disease, but the mechanism behind this relationship is not completely understood. A high concentration of Lp(a) may interfere with fibrinolysis because of the structural similarity between apo(a) and plasminogen. The aim of the present study was to examine the influence of apo(a) levels and isoforms on fibrinolytic activity in 82 subjects from 24 families in which the Lp(a) levels wereor =30 mg/dl in at least one child and one parent. Several fibrinolytic parameters, including plasmin generation by fibrin-bound tissue plasminogen activator, the lipid profile and apo(a) isoforms were studied. Subjects with high circulating Lp(a) levels (n = 44) had significantly reduced plasmin generation compared with their relatives with normal Lp(a) levels (n = 38). A significant inverse correlation between Lp(a) levels and plasmin generation was observed. The individuals with a combination of high levels of plasma Lp(a) and a major apo(a) isoformor =580 kD molecular weight show the lowest fibrinolytic activity. A high correlation was found between the levels of apo(a) isoforms in children and the levels of the corresponding parental apo(a) isoforms. We conclude that the antifibrinolytic effect of Lp(a) in subjects with two apo(a) isoforms may depend not only on the total plasma level of Lp(a) but also on the relative concentration of the small apo(a) isoform.

To evaluate the monitoring of intramucosal pH (pHi) and standard pH (pHs) during heart surgery with extracorporeal circulation (ECC) and moderate hypothermia. The correlations of pHi and pHs and the postoperative APACHE III score after surgery were analyzed.Sixteen patients with cardiac output0.4 scheduled for coronary bypass surgery, or aortic or mitral valve replacement were studied. Arterial pH (pHa), pHi and pHs were measured and the difference between pHa and pHi was calculated before starting ECC (T0), during ECC and hypothermia (T1) and after termination of ECC (T2). The APACHE III score was recorded 18 h after surgery.No significant differences between the pHi and pHs were observed in these patients. pHi was significantly higher during ECC with hypothermia (T1) than at baseline (T0). pHi and pHs were significantly correlated during the study period. There was no correlation between the APACHE III score in the immediate postoperative period and either pHi or pHs during surgery.Periods of splanchnic hypoxia (pHi7.32) during heart surgery with moderate hypothermia were not seen in patients with cardiac output0.4. pHs is a reliable measurement of pHi. There is no relation between APACHE III scores in the early postoperative period and pHi or pHs levels during surgery.

BACKGROUND: A defective hemostatic effect of plasma concentrate infusion in patients with severe von Willebrand disease (vWD) has been ascribed to the absence of platelet von Willebrand factor (vWF) STUDY DESIGN AND METHODS: The role of platelet vWF in hemostasis of severe vWD was investigated. A plateletpheresis unit (4-5 x 10 11 platelets) from a normal compatible donor was transfused before any cryoprecipitate infusion to three type 3 vWD patients and to one patient with severe type 1 vWD with low levels of platelet vWF who required replacement therapy for bleeding episodes. Autologous platelets were transfused to one of the patients with type 3 vWD. RESULTS: Partial corrections of bleeding times (14-17 min vs. baseline >30 min) were observed in all patients after the transfusion of normal platelets. During cryoprecipitate infusion, bleeding times were normalized (

This study examined ninety-six patients with essential arterial hypertension (WHO grade I-II) who had been under treatment for a period of at least one year before participating in the study. When the study began the patients received no drug treatment for one month. At the end of this washout period their basal situation was evaluated and drug treatment was begun (26 patients on calcium antagonists, 39 on beta-blockers and 31 on angiotensin converting enzyme inhibitors). The patients were evaluated again after one and two years of uninterrupted treatment with the chosen medication. The results obtained indicate that in a basal situation hypertensive patients have higher blood viscosity and erythrocyte rigidity values than the control group. Regardless of the drug treatment used, the patients experienced during the study a progressive deterioration of their hemorheological situation consisting of an increase in red blood cell rigidity and increased blood viscosity. These results indicate the importance of evaluating the hemorheological parameters of hypertensive patients and suggest that it may be advisable to include in their treatment some kind of medication that prevents progressive rheological deterioration.

The authors present a study in two groups of Wistar rats, which were given two different parenteral nutritions with two different amounts of proteins, during different periods of time (4, 7 and 11 days), with the objective of evaluating their influence on the healing of a colonic anastomosis which was performed prior to the initiation of the TPN. To asses the condition of the colonic anastomosis, we studied the rupture pressure of the colon containing the anastomosis, the hydroxyproline concentration of said anastomosis, and the histological study of the same. The results indicate that the group of animals which were fed with a hyperproteinic diet during a longer period of time, showed a better degree of healing than the rest of the study groups.

The authors describe a false outbreak of tuberculosis by contamination in sample processing.The longitudinal polymorphisms of restriction fragments (RFLPs) of 6 strains of Mycobacterium tuberculosis isolated in different patients over a three week period and which were apparently implicated in an outbreak of tuberculosis were analyzed.Four of the strains studied presented identical restriction pattern and the remaining two presented totally different patterns. Following study of the clinical histories and the epidemiologic relationships three cases of tuberculosis were confirmed. The other three strains isolated corresponded to contamination during the sampling process.In a possible outbreak of six cases of tuberculosis, molecular techniques have allowed identification of three true cases of tuberculosis and have demonstrated contamination during the sampling process in three other cases. The latter could not have been shown with the clinical and phenotypical data of the strains.

Hypertensive cardiomyopathy is nowadays the most precious, prevalent and fatal condition of all cerebral, renal and arterial complications that leads to arterial hypertension. Left ventricular hypertrophy is the basis of the macroscopic structural damage that belongs to this entity. Basically, this complication produces, in the daily practice, alterations in the systolic and dyastolic functions, myocardial ischemia and arrhythmias. At present, it is obvious that we need to take better advantage of resources to diagnose hypertensive cardiopathy, and that the cost of explorations are lower must imply an agreement between cardiologists and general practitioners. In this article, we review the resources available at general practice level for the efficient diagnosis of the complications produced by hypertensive cardiopathy.

The ability of unfractionated (UF) heparin and low-molecular-weight heparin (LMWH) to potentiate the inhibition of fibrinolytic and coagulation factors by protein C inhibitor (PCI) was studied. Inhibition of activated protein C (APC), urokinase plasminogen activator (uPA), tissue plasminogen activator (tPA), thrombin, factor Xa (Xa), factor XIa (XIa) and plasma kallikrein (KK) by PCI was found to be dependent on the size of the polysaccharide. In general, maximal stimulation was reached with UF heparin, except in the case of KK. Differences in heparin stimulation were more pronounced for thrombin, APC, uPA, tPA and XIa, whereas inactivation of Xa by PCI was less dependent on the presence of heparin, and kallikrein showed higher potentiation with LMWH than with UF heparin. The second-order rate constants for enzyme inhibition by PCI were strongly dependent on the ionic strength, and, in general, with an ionic strength higher than 0.15 the heparin stimulation of the inhibition reactions was drastically reduced. These results may explain the large discrepancies in the literature on the effect of heparin on the stimulation of enzyme inhibition by PCI. They also show that LMWH is less efficient in stimulating the PCI inhibition of APC, uPA and tPA, which could contribute to the antithrombotic effect of these enzymes.

We previously reported significantly elevated levels of plasminogen activator inhibitor type 1 (PAI-1) in plasma and placenta from pregnant women with severe pre-eclampsia, and pre-eclampsia is a frequent problem in molar pregnancies. As increases in PAI-1 may contribute to the placental alterations that occur in pre-eclampsia, we have begun to investigate changes in PAI-1 as well as PAI-2 and several other components of the fibrinolytic system in patients with trophoblastic disease. Significant increases in plasma PAI-1 and decreases in plasma PAI-2 levels were observed in molar pregnancies when compared with the levels in normal pregnant women of similar gestational age. PAI-1 antigen levels also were increased, and PAI-2 levels were decreased in placenta from women with molar pregnancies compared with placenta obtained by spontaneous abortion. Immunohistochemical analysis revealed strong positive and specific staining of PAI-1 in trophoblastic epithelium in molar pregnancies and relatively weak staining of PAI-2. No association between the distribution of PAI-1 and vitronectin was found, and no specific signal for tissue type PA, urokinase type PA, tumor necrosis factor-alpha, or interleukin-1 was detected. In situ hybridization revealed an increase in PAI-1 but not PAI-2 mRNAs in placenta from molar pregnancies in comparison with placenta from abortions. These results demonstrate increased PAI-1 protein and mRNA in trophoblastic disease and suggest that localized elevated levels of PAI-1 may contribute to the hemostatic problems associated with this disorder.

Recent studies in adults have shown that hemorrheological alterations are predictive of early cardiovascular disease, but it is unknown if they are related to hyperlipemia or are secondary to an established atherosclerotic process and if they appear during childhood.Several rheological parameters have been studied in 36 patients with familial hypercholesterolemia (FH). These patients were between 2 and 16 years of age and 12 of them were being treated with cholestyramine. Thirty-five controls (CG) were individually matched for age and sex.The FH patients treated with cholestyramine did not show significant differences in any of the six rheological parameters that were studied when compared to the other patients. Therefore, the results of the FH group were analyzed as a whole when they were compared with the CG. The following significant differences were found: Index of erythrocyte aggregation at stasis 5.0 +/- 1.2 vs 3.6 +/- 1.0 (p0.001), index of erythrocyte aggregation at low rate of blood shears 8.1 +/- 1.7 vs 6.9 +/- 1.4 (p0.001) and plasma viscosity 1.19 +/- 0.11 vs 1.16 +/- 0.04 mPA/s (p0.01). There were no significant differences in the plasma fibrinogen nor in the blood viscosity at shear rats of 230/s and 23/s. Carotic echo-doppler was taken in the HF patients which was normal, indicative of the absence of atherosclerosis lesions in the fibrous plaque phase.These results indicate that there are hemorrheological alterations in absences of established atherosclerotic lesions, which are associated with hypercholesterolemia and that emerge in the pediatric population. Therefore, research in FH patients offers new data to evaluate the atherogenic risk and its complications.

Alpha-1-antitrypsin (a-1AT) is a natural inhibitor of the elastase that is released physiologically by neutrophils in the lung. As a result of the increased neutrophil degranulation secondary to chronic epithelial inflammation in cystic fibrosis patients with chronic infections by Pseudomonas aeruginosa, there are larger amounts of elastase in airway secretions. This results in the a-1AT concentration being insufficient to inhibit the destructive proteolytic degradation, culminating in a chronic epithelial burden and a worsening of the cystic fibrosis pulmonary disease. In this preliminary study, we have evaluated the results obtained from the sputum of 4 cystic fibrosis patients treated with a-1AT (Prolastina, Bayer) in aerosol. The levels of a-1AT, neutrophil elastase, antineutrophil elastase activity, IgG, albumin and clinical parameters were measured. The concentration of sputum a-1AT was increased when compared to the same patient after 8 days with treatment (we compared means with Student's t-test and p0.05 was considered significant). We did the same with the impairment of neutrophil elastase, although we found no significant results. Nevertheless, antineutrophil elastase activity increased (p0.05). These results encourage us to continue the same treatment for a longer period of time to prevent pulmonary disease in CF subjects.

Gastrointestinal motility is altered in several clinical situations in which Total Parenteral Nutrition (TPN) is indicated. Nevertheless, the effects of TPN on motility are not well known. In this study, Wistar rats (250-280 g) were divided into two groups were defined according to the route of administration of the nutrients: Group A (with TPN: 100% of the total non-protein calories administered as glucose), and Group B (solid enteral nutrition, but with the infusion of normal saline under the same conditions as in the previous group). Each group was subjected to three different infusion times: 24 hours, 3 days, and 5 days post-intervention, after which the gastric emptying was measured by means of the phenol red test. TPN delayed emptying in all the times with respect to group B, although significant differences were only found after 3 days of infusion.

The reactivity of subendothelium generated by endothelial cells attained from the umbilical cord of a newborn girl from a patient with type I von Willebrand's disease was evaluated.Platelet adhesiveness was assessed by means of "ex vivo" blood perfusion systems (shearing coefficients from 300 to 1,300 s-1), on umbilical artery subendothelium and over the extracellular matrix (ECM) generated by cultured endothelial cells attained from the umbilical cord of a newborn baby from a type I von Willebrand mother.By means of an ELISA technique, a significant reduction of both the vWF secreted into the culture (p0.05) and of that associated with ECM (p0.05) was noticed. The two subendothelial surfaces examined supported a lesser extent of platelet adhesion than the control surfaces from healthy individuals in the perfusion tests at 1,300 s-1 (p0.05). The experimental results did not agree with the lack of clinical manifestations and laboratory abnormalities in the propositus at age 3.These findings suggest that the endothelial cells cultured from the tissues of a newborn baby from a type I von Willebrand woman expressed less vWF, at the same time confirming the importance of vWF bound to connective tissue in sustaining platelet adhesion. The data attained here illustrate the complex model of inheritance of moderate von Willebrand's disease, along with the technical limitations of cell culture studies. Such observations must be borne in mind whenever any experimental approach is performed with material attained from ill-differentiated tissues such as the umbilical cord vein.

Elevated plasma levels of type 1 plasminogen activator inhibitor (PAI-1) have been implicated in mediating the fibrin deposition and occlusive lesions that occur within the placental vasculature in preeclampsia (PE) and intrauterine growth retardation (IUGR). In this report we identify the cells within the normal-appearing villous tissue that are responsible for the local production of PAI-1 in women with PE and IUGR. Levels for another fibrinolytic inhibitor (ie, type 2 plasminogen activator inhibitor [PAI-2]) were determined for comparative purposes. Elevated levels of PAI-1 were detected in placenta extracts from PE/IUGR patients (121 +/- 38 ng/mg, n = 8) when compared with the levels in placenta extracts from normal women (43 +/- 17 ng/mg, n = 10) or women with IUGR but not PE (51 +/- 22 ng/mg, n = 11). Immunohistochemical analysis of paraffin sections showed an increased immunoreactivity for PAI-1 in the placental villous syncytiotrophoblasts from PE/IUGR women compared with the immunostaining of placental samples from the normal or IUGR group. In contrast, antigen levels and immunostaining for PAI-2 were reduced in the placentas harvested from not only the PE/IUGR women (209 +/- 144 ng/mg) but also the IUGR group (169 +/- 106 ng/mg) in comparison with the PAI-2 levels in normal placentas (535 +/- 98 ng/mg). To document that the increased immunoreactivity for PAI-1 in PE/IUGR syncytiotrophoblasts was mediated by an increased production of PAI-1 within these cells, in situ hybridization analysis was performed. A strong positive signal for PAI-1 mRNA in villous syncytiotrophoblasts from PE patients (n = 5) was obtained after 2 weeks of exposure to the NTB2 emulsion in comparison with the weak signal for PAI-1 mRNA that required a 10-week exposure of the normal placenta sections (n = 10). Northern blotting for PAI-1 mRNA showed that both transcripts (ie, 3.2 and 2.3 kb) were elevated in samples of two PE patients in comparison with the PAI-1 mRNA transcripts present in a normal placenta and an IUGR placental sample. These results show increased PAI-1 and mRNA levels in placentas from PE patients and raise the possibility that localized elevated levels of PAI-1 may play a role in the initiation of placental damage, as well as in the thrombotic complications associated with this disease.

Pyomyositis (PMS) is a primary infection of striated muscle. Recent scanty reports suggest that non-tropical PMS may differ from classical tropical PMS. To address this question, 12 cases of nontropical PMS seen at two hospitals between 1976 and 1992 were reviewed and an English-literature search of similar cases was conducted. Both the series and reported cases are pooled together and herein reported. The age distribution of the 97 patients showed 30-50 and 60-70-year peaks, with a 3:1 (male-female) ratio. Fever, high erythrocyte sedimentation rate, and muscle stiffness or inflammation were present in more than 75% of patients. Muscles of the thigh (54%), back (13%), buttock (11%), arm (9%), or chest wall (4%) were involved. Staphylococci (61%), gram-negative bacilli (16%), streptococci (12%), and fungi (2%) were isolated from muscle specimens. Human immunodeficiency virus infection, diabetes mellitus, hemopoietic disorders, and other conditions with defective neutrophil function were present in 64 patients (66%). Drainage of pus and antibiotic therapy were the standard treatments. The mortality rate reached 10%. Analysis of patients classified by the comorbid condition showed differences in age, causative microorganisms, clinical features, and death rate. It is concluded that several clinical presentations of nontropical PMS are at variance with that of tropical PMS.